This invention relates to generators for radionuclides of the kind in which a parent radionuclide, adsorbed on a column of particulate material, continuously generates by radioactive decomposition a daughter radionuclide which is periodically removed by elution from the column. This invention is mainly concerned with technetium generators, in which typically the parent radionuclide molybdenum-99 is adsorbed on a column of particulate alumina and the technetium-99m eluted using physiological saline solution. But as will appear, the invention is applicable in principle to generators of any radionuclide.
Originally, separation systems consisted of open glass columns partially filled with ion-exchange material, relying on gravity for the passage of eluent through the bed.
Closed systems, operated either by hand held syringes or by gravity drainage from suspended eluent bags, appeared in the late 1960's. This advance enabled sterile systems to become widely available for clinical applications.
The demand for simple, reliable operation and the increasing size of the market led to more automation. Evacuated or pressurised vials replaced hand pressure and gravity as the driving force behind the elution.
The chemistry of the ion-exchange column and the specific activity of the parent nuclide are paramount in determining the minimum elution volume of a generator. Careful design also plays a part.
Current .sup.99m Tc generator requirements are for a minimum elution volume of about 5 ml, and existing systems are designed to achieve this as simply as possible.
Some commercially available generators use a single 5 ml evacuated vial and a self-contained reservoir of saline. When connected to an outlet needle, this vial fills by drawing 5 ml of saline from the reservoir and through the column. The column is left wet, which may mean that reagents need to be added to the saline, or incorporated in the column, to ensure that acceptable yields of .sup.99m Tc are maintained.
Other commercially available generators use charge vials containing predetermined quantities of saline instead of the saline reservoir. In this case connection of the evacuated vial results in the whole of the contents of the charge vial being drawn through the generator into the collection vial. In this latter case the collection vial finally equilibrates to atmospheric pressure by drawing air through the system via a bleed into the charge vial. This so called "double vial" or "dry-bed" elution system requires more operations to be performed by the technician, but does have two advantages over the "single vial" system. These are that the generator bed is aerated, maintaining good yields of .sup.99m Tc, and that the collection vial contains the eluate at atmospheric pressure and is only partially filled. This last point allows the technician to remove aliquots of solution very much more easily than if he had to handle a totally filled vial.
There is, however, a need for flexibility in the collected volume of eluate to avoid subsequent high dose operations such as dispensing or diluting highly radioactive eluate. It would be convenient to be able to collect the activity in a volume greater than 5 ml when this is desired. The two existing generators described above have each been modified to achieve this.
By using a larger vial, the single vial system can be designed in a manner allowing the technician to terminate the elution after 5 ml of to allow elution to continue further, effectively diluting the eluate already collected. A valve may achieve this, or the techician may intervene by removing the collection vial when it contains the required volume. Two problems arise. Firstly, the technician must be present, close to the high dose generator, so he can "move in" at the required time. Secondly, the vial, although only partially filled, has a void space, at very low pressure. It is not as easy task to remove aliquots of solution from such a vial without first carefully venting it in an aseptic manner. Such venting may be done after removal of the vial from the generator or, possibly, by incorporation of a venting device in the generator.
An alternative method of modifying the single vial system is to employ evacuated vials of different capacities and to allow complete elution to proceed. However, a multiplicity of collection vials and possibly vial shields are needed, and the problem of completely filled vials still remains.
Very recently yet another attempt to overcome the problems of handling these completely full vials has been made. Another commercial supplier now offers the option of using partially evacuated vials with which to elute their generator. These result in a partially filled vial of eluate at atmospheric pressure, but of course the volume of the eluate has been chosen not by the technician, but by the generator supplier.
Double vial systems achieve a measure of flexibility by filling the charge vials to different volumes. Again, the requirement for an increased number of different elution components presents complications for both the technician and the generator manufacturer.
Thus, it can be seen that there are advantages and disadvantages in both the single and double vial approaches. Simplicity in operation (single vial system) can incur problems for the technician in handling collection vials conveniently and in the need for additives in saline. However, when these problems are eliminated (double vial systems), other disadvantages, namely the need for more operations and components, are substituted.